Fractionated radioimmunotherapy with 90Y-clivatuzumab tetraxetan and low-dose gemcitabine is active in advanced pancreatic cancer
Ocean AJ et al. – Fractionated radioimmunotherapy with 90Y–humanized clivatuzumab tetraxetan (hPAM4) and low–dose gemcitabine demonstrated promising therapeutic activity and manageable myelosuppression in patients with advanced pancreatic ductal carcinoma.Methods
- Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200mg/m2 weekly for 4weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2-4).
- In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5mCi/m2, 9.0mCi/m2, 12.0mCi/m2, and 15.0mCi/m2.
- In the second portion, 19 additional patients received weekly doses of 9.0mCi/m2 or 12.0mCi/m2.
- Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute's Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred.
- Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy.
- The maximum tolerated dose of 90Y-hPAM4 was 12.0mCi/m2 weekly for 3weeks for cycle 1, with ≤9.0mCi/m2 weekly for 3weeks for subsequent cycles, and that dose will be used in future trials.
- Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control).
- The median overall survival was 7.7 months for all 38 patients, including 11.8months for those who received repeated cycles (46% [6 of 13 patients] ≥1year), with improved efficacy at the higher radioimmunotherapy doses.